CN104784157A - Stable Montelukast oral film preparation - Google Patents
Stable Montelukast oral film preparation Download PDFInfo
- Publication number
- CN104784157A CN104784157A CN201510157728.XA CN201510157728A CN104784157A CN 104784157 A CN104784157 A CN 104784157A CN 201510157728 A CN201510157728 A CN 201510157728A CN 104784157 A CN104784157 A CN 104784157A
- Authority
- CN
- China
- Prior art keywords
- montelukast
- agent according
- combination
- menglusitena
- oral membrane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 title claims abstract description 27
- 229960005127 montelukast Drugs 0.000 title claims abstract description 27
- 238000002360 preparation method Methods 0.000 title abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 31
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229940079593 drug Drugs 0.000 claims abstract description 20
- 239000003381 stabilizer Substances 0.000 claims abstract description 12
- 229960001484 edetic acid Drugs 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 3
- 239000010408 film Substances 0.000 claims description 28
- 239000012528 membrane Substances 0.000 claims description 28
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 15
- 239000010409 thin film Substances 0.000 claims description 12
- 239000002671 adjuvant Substances 0.000 claims description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000004014 plasticizer Substances 0.000 claims description 6
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- QLBHNVFOQLIYTH-UHFFFAOYSA-L dipotassium;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [K+].[K+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O QLBHNVFOQLIYTH-UHFFFAOYSA-L 0.000 claims description 3
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- QZKRHPLGUJDVAR-UHFFFAOYSA-K EDTA trisodium salt Chemical compound [Na+].[Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O QZKRHPLGUJDVAR-UHFFFAOYSA-K 0.000 claims description 2
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- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 2
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- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 2
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- 235000019615 sensations Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 238000011282 treatment Methods 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a stable Montelukast oral film preparation. The oral film preparation contains an effective amount of Montelukast or pharmaceutically acceptable salts of the Montelukast, a drug stabilizer at least comprising edetic acid and/or editate as well as pharmaceutically acceptable auxiliary materials. The Montelukast oral film preparation obtained according to the formula is accurate in dose, stable in quality and capable of effectively preventing oxidization and degradation of effective components, has the advantages of bright color, good taste, capability of being quickly dissolved in an oral cavity without water, improves the administration compliance of a patient and is particularly suitable for infants and patients suffering from dysphagia.
Description
Technical field
The present invention relates to a kind of stable montelukast oral thin film formulations, belong to medical art.
Background technology
Menglusitena chemistry [R-(E)]-1-by name [[[1-[3-[2-[the chloro-2-quinoline of 7-] vinyl] phenyl-3-[2-(1-hydroxyl-1-Methylethyl) phenyl] propyl group] sulfur] methyl] cyclopropaneacetic acid sodium, structural formula is as follows:
Menglusitena is a kind of potent, selectivity leukotriene D receptor antagonist, various stimulating factor (the sulfur dioxide of energy Selective depression, motion and cold air etc.) and various allergen (pollen, soft flocks etc.) caused by the increasing of inflammatory factor leukotriene polypeptide, thus suppress speed to be sent out mutually and tardy phase inflammatory reaction, alleviate or prevent a series of air flue to react (bronchoconstriction, mucous secretion, vascular permeability increases and eosinophil accumulation), be widely used in bronchial asthma, exercise-induced asthma, the prevention of allergic rhinitis and long-term treatment, especially department of pediatrics respiratory system disease, it is the long-term control medications that domestic and international treating asthma in recent years uniquely can be applied separately except powder for inhalation.
First Menglusitena develops synthesis by MSD Corp. of the U.S. (MSD), in 1997 first in Mexico's listing, subsequently in more than 70 country's listings such as the U.S., Europe, China.Menglusitena worldwide sales in 2012 43.052 hundred million dollars, domestic 2012 annual sales amounts are 2.137 hundred million yuan, 2013 2.588 hundred million yuan, increase by 21.09% on a year-on-year basis, the large and rapid development of international and domestic market sales volume.Dosage form of having gone on the market at present comprises ordinary tablet, chewable tablet and granule.Because Menglusitena ordinary tablet must first disintegrate under one's belt could start to discharge medicine, onset is slow, takes also not aspect.And as pediatric drugs, especially for the infant within 2 years old, poor to the compliance of chewable tablet or granule, easily there is telling medicine phenomenon, be difficult to realize correct dose medication and affect the treatment, greatly affect the clinical practice of Menglusitena oral formulations in department of pediatrics.
Oral instant membrane is named again mouth molten film, is a kind of oral drugs thin film formulations at rapid oral dissolution.Compared with the oral solid formulation of other kinds, oral thin film preparation has many advantages, such as novel appearance, special taste; Taking convenience; Rapid oral dissolution, not easily to spue; Absorb quick, rapid-onset; Supplementary product consumption is few, technique is simple; Swallow convenience, can not cause and suffocate etc.In view of oral thin film preparation has plurality of advantages, therefore become one of hot fields of domestic and international preparation research and development.Current gone on the market in the world tens kinds of oral thin film preparations, such as ondansetron oral thin film, Dextromethorphan oral cavity membrane agent, risperidone orally membrane agent, donepezil hydrochloride orally membrane agent etc.
Menglusitena is developed to color is vivid, the molten membrane of the mouth of good mouthfeel, when taking without the need to water can in oral cavity flash melt, and patient can according to the quick and convenient medication of the state of an illness, greatly can improve the Compliance of patient, the patient of special suitable for baby and dysphagia takes.In addition, because oral mucosa enriches, be developed to the absorption rate that the molten membrane of mouth can improve medicine, be conducive to the rapid recovery of the patient's condition.
But, Menglusitena chemical constitution is complicated, active group is more, the impact of oxygen or illumination is being produced or be subject in storage process to formulation products, there is oxidation reaction and isomerization reaction, generate specific impurities sulfoxide and cis-isomer, and make because product thickness is thin, surface area large after the molten membrane of mouth, being more vulnerable to external environment (oxidation, high temperature, illumination) affects and degrades.If develop become the molten film preparation of mouth just must by repeatedly exploring, the well-designed unfavorable factors such as active constituents of medicine stability is bad overcoming the molten film preparation of mouth and exist.
Disclose a kind of Montelukast sodium film-like preparation in prior art, its mainly through by active constituents of medicine load acid and or alkaline film strips on, film strips becomes effervescent film after meeting water, produces a large amount of bubble, paralysis olfactory sensation and taste masking, and accelerates drug-eluting.This technology does not provide suggestion for product stability aspect.
A kind of method directly forming Menglusitena dissolving film on surface of package is also disclosed in prior art.This technology is mainly set forth the method directly forming film at surface of package, does not provide suggestion to product stability aspect.
For the stability problem of Menglusitena membrane, disclose a kind of BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) that uses in prior art and make antioxidant, coupling potassium dihydrogen phosphate and dipotassium hydrogen phosphate improve the stability of Menglusitena as antioxidant synergist simultaneously.But BHT and BHA has the response feature of phenol, the metal of trace or illumination all can make its variable color, loss of activity.Both are water-soluble all hardly, and need in technical process with an organic solvent to dissolve, and recent studies have found that, long-term taking BHA has the risk of bringing out cancer, and as a kind of pediatric drugs, security risks is higher.
The present invention is intended to select the higher stabilizing agent of a kind of safety to overcome the degraded of the molten film production of Menglusitena mouth and memory period effective ingredient, and by this product flash melt, bright-colored and taste good advantage in oral cavity, improves infant medication compliance.
Summary of the invention
For prior art Problems existing and weak point, the invention provides a kind of montelukast oral membrane agent of good stability.
The invention provides a kind of stable montelukast oral membrane agent, it is characterized in that, comprise active component montelukast or its pharmaceutically acceptable salt, drug stabilizing agent and other adjuvants pharmaceutically acceptable, described drug stabilizing agent at least comprises edetic acid and/or edetate.
Montelukast oral membrane agent of the present invention, preferably, described active component is Menglusitena.
In described oral thin film of the present invention, the percentage by weight of drug stabilizing agent is 0.01% ~ 10%, preferably 0.25% ~ 5%, more preferably 0.5% ~ 2%.
Montelukast oral membrane agent of the present invention, described edetate is selected from disodium edetate, EDTAP dipotassium ethylene diamine tetraacetate, CaEDTA, one of edetate sodium and edetate trisodium or combination in any.
Montelukast oral membrane agent of the present invention, described other adjuvants pharmaceutically acceptable comprise film former, plasticizer, coloring agent, correctives and other adjuvants.Described film former is selected from one of hypromellose, hydroxypropyl cellulose, polyvinyl alcohol, polyoxyethylene, gelatin, xanthan gum, sodium alginate or combination in any.Described plasticizer one of to be selected from Polyethylene Glycol, glycerol, propylene glycol, Polysorbate or combination in any.Described coloring agent one of to be selected from titanium dioxide, pigment, color lake or combination in any.Described correctives one of to be selected from sucralose, aspartame, stevioside, glucide, mannitol, xylitol, sorbitol, menthol, essence or combination in any.Other adjuvants described comprise antiseptic and/or saliva stimulant; Described antiseptic is selected from one of sodium benzoate, potassium sorbate, methyl hydroxybenzoate, ethyl hydroxybenzoate or combination in any; Described saliva stimulant is selected from one of citric acid, tartaric acid, malic acid, mannitol or combination in any.
Montelukast oral membrane agent of the present invention, demonstrates unusual stability after adding drug stabilizing agent of the present invention, and the degraded of active component obviously reduces.Described oral thin film 40 DEG C with under 75% relative humidities place 6 months compared with 0 day related substance without significant change, specific degradation impurity sulfoxide recruitment is no more than 0.1%, far below the Menglusitena oral formulations that goes on the market as chewable tablet import registered standard required standard limit (standard-required sulfoxide must not more than 2.5%).
Even if oral thin film of the present invention place under 60 DEG C of more violent conditions 10 days compared with 0 day related substance still without significant change, specific degradation impurity sulfoxide recruitment is still no more than 0.1%, still far below the Menglusitena oral formulations that goes on the market as chewable tablet import registered standard required standard limit (standard-required sulfoxide must not more than 2.5%).
Montelukast oral membrane agent of the present invention has following beneficial effect:
There is vivid color and good taste, be easy to be accepted by patient especially infant patient, and can not any discomfort be produced after taking;
Without the need to drinking-water can in oral cavity flash melt, and discharge active constituents of medicine, avoid patient's Tibetan medicine, tell medicine;
There is good physical property, can meet in intensity, toughness etc. the production (as processing steps such as cutting, packagings) of product, preservation, transport and Clinical practice time be convenient to take;
Possesses good medicine stability.
The molten film of montelukast mouth provided by the present invention can not only improve the Clinical practice compliance of existing listing dosage form, and can improve clinical onset of action speed, has very high clinical development and use value.Can be used for bronchial asthma, exercise-induced asthma, the prevention of allergic rhinitis and long-term treatment, especially department of pediatrics respiratory system disease.
Accompanying drawing explanation
The stripping curve comparison diagram of Fig. 1 Menglusitena of the present invention oral instant membrane and commercially available Montelukast sodium chewable tablet.
Detailed description of the invention
The present invention is further illustrated below by embodiment.Should be understood to: embodiments of the invention are only used for the present invention being described and providing, instead of limitation of the present invention, under the prerequisite of technical solution of the present invention, all belong to protection scope of the present invention to simple modifications of the present invention.
Test example 1
With reference to Montelukast sodium chewable tablet import registered standard X20010209 determination of related substances method, lucifuge operates.Chromatographic condition phenyl bonded silica is filler, and column temperature is 50 DEG C, and determined wavelength is 255nm, and flow rate of mobile phase is 1.5ml/ minute, and sampling volume is 20 μ L, and adopt linear gradient elution, concrete elution program is as follows:
Mobile phase A: the trifluoroacetic acid aqueous solution of 0.2%
Mobile phase B: methyl-acetonitrile (60:40)
| Time (minute) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 48 | 52 |
| 5 | 45 | 55 |
| 12 | 45 | 55 |
| 22 | 25 | 75 |
| 23 | 25 | 75 |
| 25 | 48 | 52 |
| 35 | 48 | 52 |
Measure, sulfoxide must not cross 2.5% in accordance with the law; Cis-isomer must not cross 0.1%; Ketone group methanol must not cross 0.1%; Other single impurity must not cross 0.1%; Total impurities must not cross 2.7%.
Embodiment 1 disodium edetate is on the impact of product stability
* use in prescription but remove in technical process.
Preparation technology: each component except Menglusitena and filmogen be under agitation dissolved or dispersed in water under lucifuge condition, add Menglusitena stirring and dissolving, must contain drug solns; Add filmogen, be stirred to and dissolve completely, obtain pastille glue; Stir deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, after heat drying, cuts into certain size, obtain the molten film of pink Menglusitena mouth.
Comparative example 1
* use in prescription but remove in technical process.
Preparation technology: each component except Menglusitena and filmogen be under agitation dissolved or dispersed in water under lucifuge condition, add Menglusitena stirring and dissolving, must contain drug solns; Add filmogen, be stirred to and dissolve completely, obtain pastille glue; Stir deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, after heat drying, cuts into certain size, obtain the molten film of pink Menglusitena mouth.
In comparative example 1, PEG400 or glycerol or polyoxyethylene sorbitan monoleate is adopted to make plasticizer respectively, when wherein PEG400 or glycerol consumption are 5% the molten film-strength of gained Menglusitena mouth and toughness poor, film is gently rolled over and is namely broken, be difficult to meet cutting or packing instructions, when consumption continues to increase to 10%, physical property is obviously improved, adopt Intelligent electronic tensil testing machine (XLW type, Jinan blue light mechanical & electrical technology company limited) to measure pull-off force and be all greater than 15N.And polyoxyethylene sorbitan monoleate consumption gained Menglusitena mouth molten film when being 5% or 10%, pull-off force is all greater than 15N, intensity and toughness good.
The sample of embodiment 1 and comparative example 1 is placed 30 days under being placed in 40 DEG C and 75% relative humidities respectively, measures in sampling in 0,15,30 day according to the method for test example 1.Result is as follows:
Result of the test shows, adopt PEG400 or glycerol or polyoxyethylene sorbitan monoleate as plasticizer respectively, place 30 days under 40 DEG C of hot conditionss, impurity sulfoxide and total impurities increase sharply; And after adding stabilizing agent disodium edetate, the generation of impurity sulfoxide obviously reduces, greatly improve the stability of product.
Embodiment 2 different amounts disodium edetate is on the impact of product stability
* use in prescription but remove in technical process.
Preparation technology: each component except Menglusitena and filmogen be under agitation dissolved or dispersed in water under lucifuge condition, add Menglusitena stirring and dissolving, must contain drug solns; Add filmogen, be stirred to and dissolve completely, obtain pastille glue; Stir deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, after heat drying, cuts into certain size, obtain the molten film of pink Menglusitena mouth.
Comparative example 2
| Title | Dry ratio |
| Menglusitena | 20.8％ |
| Hypromellose | 52.96％ |
| Hydroxypropyl cellulose | 13.24％ |
| Polyoxyethylene sorbitan monoleate | 5％ |
| Sucralose | 1％ |
| Cherry essence | 3.5％ |
| Red ferric oxide | 0.5％ |
| Titanium dioxide | 3％ |
| Purified water * |
* use in prescription but remove in technical process.
Preparation technology: each component except Menglusitena and filmogen be under agitation dissolved or dispersed in water under lucifuge condition, add Menglusitena stirring and dissolving, must contain drug solns; Add filmogen, be stirred to and dissolve completely, obtain pastille glue; Stir deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, after heat drying, cuts into certain size, obtain the molten film of pink Menglusitena mouth.
Place 30 days under the sample of embodiment 2 and comparative example 2 being placed in respectively 40 DEG C and 75% relative humidities, measure according to the method for test example 1 in sampling in 0,15,30 day.Result is as follows:
Result of the test shows, placement 30 days under 40 DEG C of hot conditionss, does not add disodium edetate prescription impurity sulfoxide and total impurities obviously increases; Add disodium edetate prescription impurity sulfoxide and total impurities only slightly increases; And disodium edetate consumption when being greater than 0.5% compared with 0 day, prescription impurity sulfoxide and total impurities are without significant change, and stability significantly improves.
The sample of another Example 1 and comparative example 1 is placed in 60 DEG C respectively and more places 10 days under drastic conditions, measures in sampling in 0,5,10 day according to the method for test example 1.Result is as follows:
Result of the test shows, placement 10 days under 60 DEG C of hot conditionss, does not add disodium edetate prescription impurity sulfoxide and total impurities obviously increases; Add 0.25% disodium edetate prescription impurity sulfoxide and total impurities increase is obviously slowed down; And disodium edetate consumption when being greater than 0.5% compared with 0 day, prescription impurity sulfoxide and total impurities only slightly increase, and stability significantly improves.
Embodiment 3 variety classes stabilizing agent is on the impact of product stability
* use in prescription but remove in technical process.
Preparation technology: each component except Menglusitena and filmogen be under agitation dissolved or dispersed in water under lucifuge condition, add Menglusitena stirring and dissolving, must contain drug solns; Add filmogen, be stirred to and dissolve completely, obtain pastille glue; Stir deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, after heat drying, cuts into certain size, obtain the molten film of pink Menglusitena mouth.
The sample of Example 3 is placed 30 days under being placed in 40 DEG C and 75% relative humidities, measures in sampling in 0,15,30 day according to the method for test example 1.Result is as follows:
Result of the test shows, add the conventional antioxidant such as BHT or BHA or sodium pyrosulfite, different prescription is placed 30 days respectively under 40 DEG C of conditions, each prescription impurity sulfoxide and total impurities all obviously increase, wherein BHT and BHA coupling slightly can reduce the generation of sulfoxide, but the degree that it improves product stability compared with disodium edetate is still lower.
Embodiment 4
* use in prescription but remove in technical process.
Preparation technology: each component except Menglusitena and filmogen be under agitation dissolved or dispersed in water under lucifuge condition, add Menglusitena stirring and dissolving, must contain drug solns; Add filmogen, be stirred to and dissolve completely, obtain pastille glue; Stir deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, after heat drying, cuts into certain size, obtain the molten film of pink Menglusitena mouth.
Place 6 months under the sample of embodiment 2 prescription III and embodiment 4 being placed in respectively 40 DEG C and 75% relative humidities, in 0,1,3, sampling in June measures according to the method for test example 1.Result is as follows:
Result of the test shows, disodium edetate or EDTAP dipotassium ethylene diamine tetraacetate used as stabilizers is adopted to obtain sample, 40 DEG C with under 75% relative humidities place 6 months compared with 0 day related substance without significant change, especially specific degradation impurity sulfoxide recruitment is no more than 0.1%, far below the Menglusitena oral formulations that goes on the market as chewable tablet import registered standard required standard limit (standard-required sulfoxide must not more than 2.5%), the safe medication of child can be ensured.
The molten film of test example 2 Menglusitena mouth dissolves time limit assay method
Appoint film 6 of getting it filled, get 1 at every turn, be placed in 37 ± 1 DEG C of artificial salivas gently, under static condition, observe this product consoluet time.
According to said method, measure the dissolving time limit of embodiment 2 prescription III and embodiment 4 sample, both results are dissolved the time limit and are all about 30s.The molten membrane of Menglusitena mouth developed reaches rapidly-soluble target.
Be placed in by above-mentioned sample on the tongue of oral cavity, the obtained molten film of Menglusitena mouth can dissolve completely in 5s-15s, release Menglusitena; The molten film of obtained Menglusitena mouth slightly sweet taste and cherry flavor in addition, taste is good, is easy to accept.
The comparison of test example 3 stripping curve
According to embodiment 2 prescription III and embodiment 4 prescription I, prepare Menglusitena oral thin film, gained thin film is cut into the molten film of Menglusitena mouth (specification 5mg) that size is 2 × 1.5cm, thickness about 50 μm, simultaneously with commercially available Montelukast sodium chewable tablet (5mg specification, Merck & Co., Inc.) medicine in contrast.With the aqueous solution 900ml containing 0.5% sodium lauryl sulphate for dissolution medium, rotating speed is 50 turns per minute, adopts the stripping curve of both paddle method mensuration.Found that, according to the dissolution rate of the molten film of Menglusitena mouth prepared by the present invention apparently higher than Montelukast sodium chewable tablet commercially available at present, concrete result of the test is shown in Fig. 1.
Claims (10)
1. a montelukast oral membrane agent, is characterized in that, comprises active component montelukast or its pharmaceutically acceptable salt, and drug stabilizing agent and other adjuvants pharmaceutically acceptable, described drug stabilizing agent at least comprises edetic acid and/or edetate.
2. montelukast oral membrane agent according to claim 1, is characterized in that, described active component is Menglusitena.
3. montelukast oral membrane agent according to claim 1, is characterized in that, is 0.01% ~ 10% at the percentage by weight of described oral thin film Chinese medicine stabilizing agent, preferably 0.25% ~ 5%, more preferably 0.5% ~ 2%.
4. montelukast oral membrane agent according to claim 1, is characterized in that, described edetate is selected from disodium edetate, EDTAP dipotassium ethylene diamine tetraacetate, CaEDTA, one of edetate sodium and edetate trisodium or combination in any.
5. montelukast oral membrane agent according to claim 1, is characterized in that, described other adjuvants pharmaceutically acceptable comprise film former, plasticizer, coloring agent, correctives and other adjuvants.
6. montelukast oral membrane agent according to claim 5, is characterized in that, described film former is selected from one of hypromellose, hydroxypropyl cellulose, polyvinyl alcohol, polyoxyethylene, gelatin, xanthan gum, sodium alginate or combination in any.
7. montelukast oral membrane agent according to claim 5, is characterized in that, described plasticizer one of to be selected from Polyethylene Glycol, glycerol, propylene glycol, Polysorbate or combination in any.
8. montelukast oral membrane agent according to claim 5, is characterized in that, described coloring agent one of to be selected from titanium dioxide, pigment, color lake or combination in any.
9. montelukast oral membrane agent according to claim 5, is characterized in that, described correctives one of to be selected from sucralose, aspartame, stevioside, glucide, mannitol, xylitol, sorbitol, menthol, essence or combination in any.
10. montelukast oral membrane agent according to claim 5, is characterized in that, other adjuvants described comprise antiseptic and/or saliva stimulant; Described antiseptic is selected from one of sodium benzoate, potassium sorbate, methyl hydroxybenzoate, ethyl hydroxybenzoate or combination in any; Described saliva stimulant is selected from one of citric acid, tartaric acid, malic acid, mannitol or combination in any.
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| CN109843273A (en) * | 2016-10-20 | 2019-06-04 | 因特根克斯公司 | The device and method for treating illness relevant to neuroinflamation |
| CN110381931A (en) * | 2017-03-30 | 2019-10-25 | 因特根克斯公司 | The treatment method and device of the bioavilability of improved leukotriene receptor antagonists |
| EP3426235A4 (en) * | 2016-03-11 | 2019-11-13 | Intelgenx Corp. | Montelukast transmucosal film |
| CN114557981A (en) * | 2022-03-02 | 2022-05-31 | 山东新时代药业有限公司 | Montelukast oral cavity dissolving film agent and preparation process thereof |
| US11672792B2 (en) | 2017-07-05 | 2023-06-13 | Enlitisa (Shanghai) Pharmaceutical Co., Ltd | Topical formulations comprising montelukast and combinations with mussel adhesive proteins |
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| CN104168892A (en) * | 2011-12-26 | 2014-11-26 | Sk化学公司 | Films containing montelukast or a pharmaceutically acceptable salt thereof for oral administration |
| CN102973532A (en) * | 2012-12-28 | 2013-03-20 | 南京瑞尔医药有限公司 | Stable montelukast sodium tablet and preparation method thereof |
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| EP3426235A4 (en) * | 2016-03-11 | 2019-11-13 | Intelgenx Corp. | Montelukast transmucosal film |
| CN109843273A (en) * | 2016-10-20 | 2019-06-04 | 因特根克斯公司 | The device and method for treating illness relevant to neuroinflamation |
| CN110381931A (en) * | 2017-03-30 | 2019-10-25 | 因特根克斯公司 | The treatment method and device of the bioavilability of improved leukotriene receptor antagonists |
| US11672792B2 (en) | 2017-07-05 | 2023-06-13 | Enlitisa (Shanghai) Pharmaceutical Co., Ltd | Topical formulations comprising montelukast and combinations with mussel adhesive proteins |
| CN114557981A (en) * | 2022-03-02 | 2022-05-31 | 山东新时代药业有限公司 | Montelukast oral cavity dissolving film agent and preparation process thereof |
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| CN104784157B (en) | 2018-06-26 |
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